Diseases of the endocrine glands highlight the importance of hormonal and nutritional factors in the regulation of metabolism in human beings. The nutritional alterations affect each and every aspect of the functioning of the endocrine glands leading to serious disorders. The last century was marked by the classical deficiency disorders, such as goiter, cretinism, hypothyroidism, and rickets. Industrialization coupled with increased availability of junk food leads to the epidemic of different nutritional endocrine disorders, such as obesity, metabolic syndrome, and diabetes. Endocrine disruptors are the new kids on the block with a variety of implications ranging from obesity to pubertal disorders. We give a concise outlook on various nutritional endocrine disorders in this review.

Nutrition and endocrinology are linked from time immemorial with the premise that adequate nutrition is required for statural growth. The spectrum is expanded later with recognition of thyroid disorders resulting from iodine deficiency in certain geographic areas. [1] Further the link between rickets and calcium and vitamin D deficiency was established leading to fortification of many food substances with vitamin D. [2] The association between childhood obesity leading to the metabolic consequences in adult life is a matter of great concern during the last couple of decades. [3] The last decade is buzzing with the effects of endocrine disruptors on various hormonal axes affecting the puberty and other functions in the latest generation. [4] It is evident from these reports that the endocrine gland function is affected by nutritional alterations.

Nutritional endocrine disorders are characterized by alteration in the function or structure of the endocrine glands with resulting clinical consequences due to the deficiency or excess of a dietary compound. The nutrients in the food are subdivided into major and minor nutrients. Carbohydrates, proteins, and fats constitute the major nutrients, whereas vitamins and minerals form the minor nutrients. Most of the nutritional endocrine disorders result from nutritional deficiency barring few disorders, such as obesity and diabetes, due to nutrient excess. From an era of nutrient deficiency disorders, such as short stature and rickets, we have evolved into nutrient excess conditions, such as obesity and metabolic syndrome. The spectrum of nutritional endocrine disorders is summarized in [Table 1]. In this article, we shall give a concise overview of the important nutrient endocrine disorders and relevant dietary recommendations.

Micronutrients, mostly iodine and selenium, are required for thyroid hormone synthesis and function. Iodine is an essential component of thyroid hormones and its deficiency is considered as the most common cause of preventable brain damage in the world. [1] Iodine deficiency disorders include goiter, hypothyroidism, and mental retardation, and are shown in [Table 2]. Iodine supplementation, in the form of iodized salt resulted in decrease of these disorders in the last few decades. Increased carbohydrate content in the diet results in a higher T3 production, leading to increased iodine requirement. The higher iodine requirement exceeds the availability of iodine from environmental sources in many regions of the world, resulting in the development of iodine deficiency disorders. Iodine excess is implicated in predisposition to autoimmune thyroid disease and rarely hyperthyroidism, which also known as Jod-Basedow phenomenon. [5]

Three different selenium-dependent iodothyronine deiodinases (types I, II, and III) are essential in physiology of thyroid hormones, making selenium an essential micronutrient for optimal thyroid function. Furthermore, selenium is found as selenocysteine in the catalytic center of enzymes protecting the thyroid from free radical damage. Substances introduced with food, such as thiocyanate and isoflavones interfere with micronutrients and influence thyroid function. Other micronutrients that have an essential role in thyroid function are iron, perchlorate, zinc, and vitamin A. [6] A deficiency of these micronutrients alone or together affects iodine nutrition and thyroid function, highlighting the importance of a balanced nutritious diet.

Nutritional bone disorders

Nutrition plays a major role in the prevention and treatment of bone disorders, such as rickets, osteomalacia, and osteoporosis. [2] The macronutrients of major importance are dietary protein intake and the micronutrients of greatest importance are calcium and vitamin D. Vitamin D deficiency in childhood predisposes to osteoporosis and nonskeletal disorders, such as diabetes mellitus, cancer, and multiple sclerosis. [7] The other micronutrient needs for optimum bone health are explained in [Table 3].

Adequate calcium intake is the most critical nutritional factor to achieve optimal peak bone mass. Vitamin D is essential for intestinal calcium absorption. Low calcium in the setting of vitamin D deficiency leads to stimulation of parathyroid gland, which leads to release of calcium and phosphorus from the bone. [2] The cumulative effects are decreased bone mineralization and disorganized growth leading to characteristic deformities. Milk and dairy products are an optimal source of calcium and sunlight for vitamin D. Nutritional rickets is a disease of growing bones caused by calcium and vitamin D deficiency or both in combination. Rickets is characterized by delayed fontanelle closure, enlarged wrists, rickety rosary, craniotabes, enamel hypoplasia, and skeletal deformities. A daily intake of 400-800 IU of vitamin D along with 1000 mg of calcium is recommended to prevent the nutritional bone disorders. Rich sources of vitamin D include fatty fish, fish-liver oils (cod liver oil), and liver and dietary sources of calcium are dairy products (milk, yogurt, cheese), dark green vegetables, and nuts.

Osteoporosis

Osteoporosis is a disease characterized by low bone mass, microarchitectural deterioration leading to increased fracture risk of the bones. In addition to calcium and vitamin D, other micronutrients and their relevant functions in bone health are shown in [Table 3]. Excess dietary protein is detrimental to bone health due to hypercalciuria and acidosis. [8] Hypercalciuria is due to increased glomerular filtration rate and decreased tubular calcium reabsorption, resulting in negative calcium balance.

Fluorosis

Fluorosis is a skeletal disease caused by the consumption of excess fluoride. The common cause in India is the consumption of ground water from bore wells, which have an unacceptably high fluoride levels. [9] The disease is endemic in certain southern states, such as Andhra Pradesh. Excess fluorine forms an insoluble salt-like calcium fluoride leading to increased bone density but decreased bone strength. The disease is characterized by pain and stiffness of joints, arthritis, enamel abnormalities, skeletal deformities, and other systemic effects. The best way to prevent the problem is defluoridation of water prior to consumption.

Nutritional metabolic disorders including diabetes

The world is grappling with increased prevalence of obesity, diabetes, and associated metabolic disorders in children and adults. The primary reason for this excess prevalence is due to increased calorie consumption on a background genetic predisposition. Although obesity is the leading nutritional endocrine disorder we shall restrict our discussion to other metabolic disorders, including diabetes:

Type-1 diabetes

The development of type-1 diabetes mellitus is thought to be related to environmental trigger factors acting upon a background of genetic predisposition. Apart from congenital rubella infection, other infections, toxins, and dietary factors are considered as causative factors. The nutritional factors proposed to increase the risk of type-1 diabetes mellitus are the early introduction of bovine milk, and cereals in less than 3 months age infants. [10]

Fibrocalcific pancreatic disease (FCPD)

Malnutrition-related diabetes mellitus is an entity described from Asia and Sub-Saharan Africa and was subdivided into protein-deficient diabetes mellitus and fibrocalculous pancreatic disease. The dietary factors claimed to have a pathophysiologic role in FCPD are cyanide toxicity from consumption of cassava, another starchy root Ensete ventricosum in Africa, and cabbage intake. [11] The recent WHO classification of diabetes merged the two entities and retained the FCPD (also known as type-3C diabetes), which has the following characteristics:

Prevalence in a defined geographic area

Consumption of low proteins < 30 g per day

Intake of dietary compounds as mentioned above

Onset at less than 30 years of age

Insulin requirement for the control of hyperglycemia but ketosis resistance

Chromium is a common element in the earth's crust and seawater. It is a critical cofactor in the insulin action and deficiency results in hyperglycemia. [12] Trivalent chromium is found in a wide range of foods, including egg yolks, whole-grain products, cereals, coffee, nuts, green beans, broccoli, meat, and some brands of wine and beer. A few studies have reported beneficial effects of chromium supplementation on the diabetes and glycemic control.

Nutritional gonadal disorders

Nutritional excess state in last century lead to a secular trend of increased height and early puberty in children. This phenomenon is partly explained by the effects of various endocrine disruptors. [4] Industrialization leads to increased pollutants and contaminants in the nature, which are acquired into the human body through dietary constituents. Several endocrine disruptors, such as phytoestrogens, topical, and natural estrogens, pesticides, industrial chemicals, and phthalates have been identified as agents affecting pubertal development. The mechanism of action of endocrine disruptors could be estrogenic/androgenic/antiestrogenic and antiandrogenic. [13] Depending on their mechanism, they lead to precocious puberty, delayed puberty, or sexual differentiation disorders.

Anorexia nervosa is a psychiatric disorder of nutritional deficiency with a variety of endocrine manifestations affecting adrenal, gonadal, and thyroidal axes. [14] The effects of starvation are extensive and are summarized in [Table 4]. This nutritional psychiatric disorder is characterized by hypercortisolemia, growth hormone (GH) resistance, hypogonadism, bone loss, and refeeding syndrome during nutritional rehabilitation. Although most endocrinopathies recover with feeding, certain effects, such as short stature, bone loss, and infertility may be longlasting. [15]

Statural growth of a child is dependent on the genetic potential, environmental influences, and underlying disease condition. Malnutrition is one of the common causes of short stature in early parts of the 20th century and is still prevalent in some developing countries. [16] Marasmus is a deficiency of calories including proteins, whereas kwashiorkor is characterized by protein deficiency alone. In nutritional short stature the decrease in weight precedes the linear growth failure. The impaired growth is due to the state of GH resistance with normal GH and reduced IGF-1 levels. [17] Growth hormone is unable to stimulate the transcription of growth factors with inadequate nutritional support and occasionally the levels of GH are lower in states of chronic malnourishment. Regular nutritional counseling, including replacement of deficient nutrients is essential in children who are receiving GH supplements. Zinc deficiency syndrome alone in children may result in anorexia and poor growth. [18]

Conclusion

The adoption of healthy eating practices is essential in the efforts to improve health and prevent disease. The detrimental effects of nutrient deficiencies are fast replaced by the deleterious consequences of nutrient excess in recent times. Developing countries, such as India, are at crossroads facing the burden of both these extremes. Radical reforms and public education are important involving all the stakeholders to devise policies to overcome the burden of nutritional endocrine disorders.